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Polymorphisms in Iron Homeostasis Genes and Urinary Cadmium Concentrations among Nonsmoking Women in Argentina and Bangladesh.

Rentschler, Gerda LU ; Kippler, Maria ; Axmon, Anna LU orcid ; Raqib, Rubhana ; Ekström, Eva-Charlotte ; Skerfving, Staffan LU ; Vahter, Marie and Broberg Palmgren, Karin LU orcid (2013) In Environmental Health Perspectives 121(4). p.467-472
Abstract
BACKGROUND: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cadmium is absorbed by iron transporters. OBJECTIVES: To evaluate the impact of iron homeostasis genes (divalent metal transporter 1 SLC11A2; transferrin TF; transferrin receptors TFR2 and TFRC; ferroportin SLC40A1) on Cd accumulation. METHODS: Subjects were non-smoking women living in the Argentinean Andes [n=172; median urinary Cd (U-Cd)=0.24 µg/L] and Bangladesh (n=359; U-Cd=0.53 µg/L) with Cd exposure mainly from food. U-Cd and Cd in whole blood or erythrocytes (Ery-Cd) was measured by ICPMS. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n=72) with Illumina DirectHyb... (More)
BACKGROUND: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cadmium is absorbed by iron transporters. OBJECTIVES: To evaluate the impact of iron homeostasis genes (divalent metal transporter 1 SLC11A2; transferrin TF; transferrin receptors TFR2 and TFRC; ferroportin SLC40A1) on Cd accumulation. METHODS: Subjects were non-smoking women living in the Argentinean Andes [n=172; median urinary Cd (U-Cd)=0.24 µg/L] and Bangladesh (n=359; U-Cd=0.53 µg/L) with Cd exposure mainly from food. U-Cd and Cd in whole blood or erythrocytes (Ery-Cd) was measured by ICPMS. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n=72) with Illumina DirectHyb HumanHT-12 v4.0. RESULTS: TFRC rs3804141 was consistently associated with U-Cd. In the Andeans, mean U-Cd concentrations were 22% (95% CI: -2, 51%) and 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In Bangladesh, mean U-Cd concentrations were 22% (95% CI: 1, 48%) and 58% (95% CI: -3, 157%) higher in women with GA and AA versus GG genotype, respectively (adjusted for age and plasma ferritin in both groups; p for trend 0.006 [Andes] and 0.009 [Bangladesh]). TFRC expression in blood was negatively correlated with plasma ferritin (rS=-0.33, p=0.006), and positively correlated with Ery-Cd (significant at ferritin concentrations <30 µg/L only, rS=0.40, p=0.046). Rs3804141 did not modify these associations or predict TFRC expression. Cd was not consistently associated with any of the other polymorphisms evaluated. CONCLUSIONS: One TFRC polymorphism was associated with urine Cd concentration, a marker of Cd accumulation in the kidney, in two very different populations. The consistency of the findings supports the possibility of a causal association. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Environmental Health Perspectives
volume
121
issue
4
pages
467 - 472
publisher
National Institute of Environmental Health Sciences
external identifiers
  • wos:000323706100031
  • pmid:23416510
  • scopus:84875876181
  • pmid:23416510
ISSN
1552-9924
DOI
10.1289/ehp.1205672
language
English
LU publication?
yes
id
714618d7-d038-4b2d-b02e-89cdc0b50535 (old id 3559677)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23416510?dopt=Abstract
date added to LUP
2016-04-01 10:34:32
date last changed
2022-01-26 00:33:51
@article{714618d7-d038-4b2d-b02e-89cdc0b50535,
  abstract     = {{BACKGROUND: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cadmium is absorbed by iron transporters. OBJECTIVES: To evaluate the impact of iron homeostasis genes (divalent metal transporter 1 SLC11A2; transferrin TF; transferrin receptors TFR2 and TFRC; ferroportin SLC40A1) on Cd accumulation. METHODS: Subjects were non-smoking women living in the Argentinean Andes [n=172; median urinary Cd (U-Cd)=0.24 µg/L] and Bangladesh (n=359; U-Cd=0.53 µg/L) with Cd exposure mainly from food. U-Cd and Cd in whole blood or erythrocytes (Ery-Cd) was measured by ICPMS. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n=72) with Illumina DirectHyb HumanHT-12 v4.0. RESULTS: TFRC rs3804141 was consistently associated with U-Cd. In the Andeans, mean U-Cd concentrations were 22% (95% CI: -2, 51%) and 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In Bangladesh, mean U-Cd concentrations were 22% (95% CI: 1, 48%) and 58% (95% CI: -3, 157%) higher in women with GA and AA versus GG genotype, respectively (adjusted for age and plasma ferritin in both groups; p for trend 0.006 [Andes] and 0.009 [Bangladesh]). TFRC expression in blood was negatively correlated with plasma ferritin (rS=-0.33, p=0.006), and positively correlated with Ery-Cd (significant at ferritin concentrations &lt;30 µg/L only, rS=0.40, p=0.046). Rs3804141 did not modify these associations or predict TFRC expression. Cd was not consistently associated with any of the other polymorphisms evaluated. CONCLUSIONS: One TFRC polymorphism was associated with urine Cd concentration, a marker of Cd accumulation in the kidney, in two very different populations. The consistency of the findings supports the possibility of a causal association.}},
  author       = {{Rentschler, Gerda and Kippler, Maria and Axmon, Anna and Raqib, Rubhana and Ekström, Eva-Charlotte and Skerfving, Staffan and Vahter, Marie and Broberg Palmgren, Karin}},
  issn         = {{1552-9924}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{467--472}},
  publisher    = {{National Institute of Environmental Health Sciences}},
  series       = {{Environmental Health Perspectives}},
  title        = {{Polymorphisms in Iron Homeostasis Genes and Urinary Cadmium Concentrations among Nonsmoking Women in Argentina and Bangladesh.}},
  url          = {{https://lup.lub.lu.se/search/files/1958028/3789314.pdf}},
  doi          = {{10.1289/ehp.1205672}},
  volume       = {{121}},
  year         = {{2013}},
}